Therapeutic Effects of Crocin Nanoparticles Alone or in Combination with Doxorubicin against Hepatocellular Carcinoma In vitro.

IF 2.6 4区医学 Q3 CHEMISTRY, MEDICINAL Anti-cancer agents in medicinal chemistry Pub Date : 2024-10-09 DOI:10.2174/0118715206327654240823074318

Noha S Basuony, Tarek M Mohamed, Doha M Beltagy, Ahmed A Massoud, Mona M Elwan

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Abstract

Objective: Crocin (CRO), the primary antioxidant in saffron, is known for its anticancer properties. However, its effectiveness in topical therapy is limited due to low bioavailability, poor absorption, and low physicochemical stability. This study aimed to prepare crocin nanoparticles (CRO-NPs) to enhance their pharmaceutical efficacy and evaluate the synergistic effects of Cro-NPs with doxorubicin (DOX) chemotherapy on two cell lines: human hepatocellular carcinoma cells (HepG2) and non-cancerous cells (WI38).

Methods: CRO-NPs were prepared using the emulsion diffusion technique and characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), Zeta potential, and Fourier transform infrared spectroscopy (FT-IR). Cell proliferation inhibition was assessed using the MTT assay for DOX, CRO, CRO-NPs, and DOX+CRO-NPs. Apoptosis and cell cycle were evaluated by flow cytometry, and changes in the expression of apoptotic gene (P53) and autophagic genes (ATG5 & LC3) were analyzed using real-time polymerase chain reaction.

Results: TEM and SEM revealed that CRO-NPs exhibited a relatively spherical shape with an average size of 9.3 nm, and zeta potential analysis indicated better stability of CRO-NPs compared to native CRO. Significantly higher antitumor effects of CRO-NPs were observed against HepG2 cells (IC50 = 1.1 mg/ml and 0.57 mg/ml) compared to native CRO (IC50 = 6.1 mg/ml and 3.2 mg/ml) after 24 and 48 hours, respectively. Annexin-V assay on HepG2 cells indicated increased apoptotic rates across all treatments, with the highest percentage observed in CRO-NPs, accompanied by cell cycle arrest at the G2/M phase. Furthermore, gene expression analysis showed upregulation of P53, ATG5, and LC3 genes in DOX/CRO-NPs co-treatment compared to individual treatments. In contrast, WI38 cells exhibited greater sensitivity to DOX toxicity but showed no adverse response to CRONPs.

Conclusion: Although more in vivo studies in animal models are required to corroborate these results, our findings suggest that CRO-NPs can be a potential new anticancer agent for hepatocellular carcinoma. Moreover, they have a synergistic effect with DOX against HepG2 cells and mitigate the toxicity of DOX on normal WI38 cells.

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Crocin 纳米粒子单独或与多柔比星联合使用对肝细胞癌的体外治疗效果。

目的：藏红花中的主要抗氧化剂藏红花苷（CRO）因其抗癌特性而闻名。然而，由于生物利用度低、吸收性差和理化稳定性低，其局部治疗效果有限。本研究旨在制备藏红花苷纳米颗粒（CRO-NPs），以提高其药效，并评估藏红花苷纳米颗粒与多柔比星（DOX）化疗对两种细胞系：人肝癌细胞（HepG2）和非癌细胞（WI38）的协同作用：采用乳液扩散技术制备了 CRO-NPs，并通过透射电子显微镜（TEM）、扫描电子显微镜（SEM）、Zeta 电位和傅立叶变换红外光谱（FT-IR）对其进行了表征。采用 MTT 法评估 DOX、CRO、CRO-NPs 和 DOX+CRO-NPs 对细胞增殖的抑制作用。流式细胞术评估了细胞凋亡和细胞周期，实时聚合酶链反应分析了凋亡基因（P53）和自噬基因（ATG5 和 LC3）的表达变化：TEM和SEM显示，CRO-NPs呈相对球形，平均尺寸为9.3 nm，zeta电位分析表明与原生CRO相比，CRO-NPs具有更好的稳定性。与原生 CRO（IC50 = 6.1 毫克/毫升和 3.2 毫克/毫升）相比，CRO-NPs 在 24 小时和 48 小时后对 HepG2 细胞的抗肿瘤效果显著更高（IC50 = 1.1 毫克/毫升和 0.57 毫克/毫升）。对 HepG2 细胞进行的 Annexin-V 检测表明，所有处理的细胞凋亡率都有所上升，其中 CRO-NPs 的凋亡率最高，同时细胞周期停滞在 G2/M 阶段。此外，基因表达分析表明，与单独处理相比，在 DOX/CRO-NPs 联合处理中，P53、ATG5 和 LC3 基因上调。相比之下，WI38 细胞对 DOX 的毒性更敏感，但对 CRONPs 没有不良反应：尽管还需要在动物模型中进行更多的体内研究来证实这些结果，但我们的研究结果表明，CRO-NPs 可作为一种潜在的肝细胞癌抗癌新药。此外，CRO-NPs 与 DOX 对 HepG2 细胞有协同作用，并能减轻 DOX 对正常 WI38 细胞的毒性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Anti-cancer agents in medicinal chemistry ONCOLOGY-CHEMISTRY, MEDICINAL

CiteScore

5.10

自引率

3.60%

发文量

323

审稿时长

4-8 weeks

期刊介绍： Formerly: Current Medicinal Chemistry - Anti-Cancer Agents. Anti-Cancer Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of anti-cancer agents. Each issue contains a series of timely in-depth reviews and guest edited issues written by leaders in the field covering a range of current topics in cancer medicinal chemistry. The journal only considers high quality research papers for publication. Anti-Cancer Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in cancer drug discovery.